Background/aim:The reduction in effectiveness and efficiency of orthodox drugs in malaria treatments due to resistance has resulted in extensive use of plants for the treatment of periodic fevers and malaria in endemic countries. A standardized fractionated acetone-water extract from leaves(IRAB), of the neem tree (Azadirachta indica) has previously been reported to have strong antimalarial activity against Plasmodium falciparum in an in-vitro assays.However, there are no reports of its antimalarial activity in-vivo. We therefore, tested the efficacy of IRAB in-vivo in mice infected with Plasmodium yoelii. \nMethods: Using the 4–day antimalarial suppressive method, two experiments were carried out using four groups of 8 mice each. They were inoculated intraperitoneally, on day 0, with 0.2 mL of infected blood containing 107 Plasmodium yoelii parasitized erythrocytes.Two hours post-parasite inoculation, IRAB was administered to three groups of mice by oral gavage, twice daily for four consecutive days as follows; A(10mg/kg); B(30mg/kg); C(90mg/kg) IRAB.The control group (D) was similarly treated with phosphate buffered saline (pH 6.5). \nResults:Treatment with IRAB significantly reduced (p<0.0001) the parasitaemia in a dose-dependent manner.The control group had a mean parasitaemia of 16.7±4.5 while parasitaemia in groups treated with 10mg/kg, 30mg/kg and 90mg/kg IRAB was 11.9±4.7, 7.1±3.9, and 4.5±1.7 with corresponding parasite suppression of 29.0%, 57.5%,and 73.4%,respectively. In both experiments, seven mice survived in the control group (D) while in the groups treated with IRAB (A, B, C), 11, 13, and 16 mice survived, respectively. \nConclusion:These findings demonstrate that IRAB suppressed parasitaemia and enhanced the survival rate of Plasmodium yoelii infected mice.